Fear of needles is distressing in itself but can also lead to avoidance of vaccinations, blood donation, and medical tests and treatments. Working with adolescents with needle fears, we developed an automated virtual reality (VR) therapy. We set out to evaluate its efficacy.

We conducted an initial proof-of-concept cohort study followed by a Phase II randomised controlled trial. Participants were included if they were 12-15 years old and had significant needle fears that they would like treated. The proof-of-concept testing was a pre- to post-cohort study. To proceed to an RCT an effect size of at least 0.6 on the Injection Phobia Scale - Anxiety (child version) (IPS) was required. The Phase II test was a parallel group, single-blind, randomised controlled trial in one centre in England. Participants were randomly assigned (1:1) to either the VR therapy or no treatment, using a permuted blocks algorithm with randomly varying block size. The VR therapy was provided in approximately three sessions over two to three weeks. The trial assessor was masked to group allocation. Outcomes were assessed at 0, 3 (end of treatment) (primary endpoint), and 6 weeks. The primary outcome was needle fear, assessed by the IPS. Outcome analyses were done in the intention-to-treat population. Moderation and mediation tests were also planned. The RCT was prospectively registered with the ISRCTN registry, ISRCTN74002253.

From March 26th, 2024, to June 7th, 2024, 12 participants (5 [42%] males; 6 [50%] females, 1 [8%] prefer not to say, mean age 13.4 years [SD = 0.8, range 12-15]; 10 [83%] White, 1 [8%] other, 1 [8%] prefer not to say) were recruited for the cohort study. After the VR therapy, needle fears as assessed by the IPS reduced on average by 15.2 points [95% C.I. 9.2, 21.1, n = 11, Cohen's d = 1.5]. There were no serious adverse events. The RCT could therefore proceed. From October 28th, 2024, to July 15th, 2025, 60 participants (26 [43%] males; 32 [53%] females, 2 other [3%], mean age 13.4 years [SD = 0.9, range 12-15]; 57 [95%] White, 3 [5%] other) were recruited for the RCT. Compared with no treatment, there was strong evidence that VR therapy led to a reduction in needle fears (adjusted mean difference = -14.07, 95% C.I. -17.40, -10.73, p < 0.001, n = 60, Cohen's d = 1.34). The benefits were maintained at follow-up (adjusted mean difference = -14.67, 95% C.I. -18.00, -11.33, p < 0.001, n = 60, Cohen's d = 1.39). There were no serious adverse events.

An automated VR therapy, which is potentially scalable, had efficacy in reducing self-reported needle fears in adolescents. Given that this is an age at which people often have a formative experience of medical procedures, it is an important time to reduce needle fears. The intervention requires testing in a Phase III clinical trial. A key focus would be assessing whether the VR therapy increases vaccine uptake in young people who have initially refused due to needle fears.

Beryl Alexander Charity and the NIHR Oxford Health Biomedical Research Centre and NIHR Oxford Biomedical Research Centre.

BH4 deficiencies may occur with or without hyperphenylalaninemia (HPA). If identified early through neonatal screening for PKU, the clinical follow-up aims to prevent the onset of typical disease symptoms. In contrast, for the conditions not associated with HPA, diagnosis usually occurs once symptoms manifest, and follow-up focuses on monitoring the treatment's effectiveness in restoring normal neurological function. Except for pterin-4-alpha-carbinolamine dehydratase defect (PCCDd), the core symptoms and natural course of these diseases involve neurodevelopmental impairment and movement disorders. Current information on clinical follow-up and outcome comes from retrospective observational studies, with standardized measures used in only a few of them. Serial clinical observations focusing on the two most consistent areas of neurological impairment are the best predictors of outcome and the main follow-up targets. Available clinical data, often aggregating early- and late-treated patients, show that the best clinical outcome occurs in autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (AD-GTPCHd). In contrast, for recessive conditions, prognosis is variably associated with both the timing of treatment (autosomal recessive [AR]-GTPCHd, 6-pyruvoyltetrahydropterin synthase [PTPS]d, sepiapterin [SR]d, q-dihydropyridine reductase [DHPR]d) and the severity of metabolic derangement (AR-GTPCHd, PTPSd). Neurocognitive, psychiatric, and sleep disorders are currently underestimated and can occur in children and adults, affecting social adaptation and quality of life. Among metabolic alterations, blood Phe levels, when altered, warrant regular monitoring. CSF evaluation can be considered in subjects unresponsive to treatment or with an unexpected clinical course. CSF 5-MTHF monitoring should be reserved for patients with DHPRd experiencing neurological deterioration and seizures. Monitoring prolactin levels, when altered, may assist in personalizing pharmacological treatment. Serum magnesium and glucose are metabolic markers that should be assessed in PDCCd. Brain MRI monitoring is recommended for patients experiencing unusual courses, epilepsy, and neurological deterioration (particularly in PTPSd and DHPRd). A DAT scan is advised for those with AD-GTPCH who present or develop Parkinsonism, and EEG monitoring should be conducted for every patient with epilepsy or suspected seizures. For future clinical studies, it is mandatory that the clinical assessment adopt standardized tools that score impairment across neurological and behavioral domains, taking the patient's age into account.

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=1144143, identifier (CRD420251144143).

HIV-related stigma adversely impacts people with HIV. As part of a systematic literature review (SLR) to evaluate 6 research questions on HIV-related stigma among people with HIV, data from studies examining its prevalence and association with clinical and quality of life (QoL) outcomes are presented.

Searches were conducted in MEDLINE® and Embase® via the OVID platform from May 2020 to May 2023 for prevalence and from database inception to May 2023 for the other 5 research questions. Relevant conferences, SLR bibliographies, and websites were searched from January 2021 to June 2023. Records were independently screened by 2 reviewers until ≥90% inter-rater reliability was achieved. Data were extracted by 1 reviewer and validated by another.

The reported prevalence of HIV-related stigma was broad across multiple stigma types and geographic regions, ranging from 11% to 94%. Most identified studies reported significant associations between higher HIV-related stigma levels and reduced HIV-specific healthcare engagement and retention (8/11), suboptimal antiretroviral therapy adherence (16/20), unsuppressed viral load (10/14), high levels of substance use (3/4), and suboptimal mental health (28/30). Most identified studies reported significant associations between higher HIV-related stigma levels and poorer QoL (23/27).

The substantial evidence identified by this SLR suggests that HIV-related stigma is a significant challenge for people with HIV and negatively impacts QoL, mental health, and clinical outcomes. These findings underscore the importance of integrating stigma considerations into the dialogue between physicians and people with HIV to foster shared decision-making for treatment and support.

Research in child and adolescent mental health stands at an inflection point: the burden of psychiatric illness is global, heterogeneous, and dynamic, whereas our evidence base often remains limited and insufficiently responsive to patient needs. To meaningfully improve outcomes for youth and families globally and at scale, innovation in child and adolescent mental health research must extend beyond developing new treatments to encompass how we design, measure, and disseminate research. Continued innovation is essential to build on the existing corpus of knowledge and to ensure that research keeps pace with real-world clinical and public health priorities.

Diagnostic MRI evaluation of temporal lobe epilepsy (TLE) depends on the subjective visual interpretation of MRI images. These interpretations could be enhanced by quantitative artificial intelligence (AI) support tools. Humans often make sequential and conditional decisions during their radiological interpretations, such as whether an abnormality is present and, if present, characterizing the abnormality. It is not known whether it is superior to train AI to treat every decision separately in a similar step-wise manner or to train a model holistically on all decisions simultaneously. Here, we analysed three large epilepsy MRI datasets [n = 3676, 2320 people with epilepsy and 1356 healthy controls (HC)] to perform two tasks: (i) establish the presence of a TLE pattern on MRI and (ii) determine TLE pattern lateralization. We compared Step-wise models that independently classify TLE versus HC and lateralize patients as left TLE (L-TLE) or right TLE (R-TLE), against a simultaneous model trained to distinguish all three classes in a single step. To do this, 3D volumetric T1-weighted images were input into an EfficientNetV2 model multiple times to ensure reproducibility of results. Class prediction, model classification confidence and saliency maps were output for interpretability. Step-wise models outperformed the Simultaneous model on both tasks (both Ps < 0.001), with an average ∼2.8% accuracy increase for discriminating HC from TLE and an average 12.7% accuracy increase for distinguishing L-TLE from R-TLE. For both the Step-wise and Simultaneous models, important features discriminating TLE from HC included the known TLE limbic pattern involving the hippocampus, parahippocampal cortical regions, cingulate cortex and lateral temporal regions. However, there was less concordance between the Step-wise and Simultaneous models for the L-TLE versus R-TLE task (all Fisher's Zs > 10.5, Ps < 0.001); the Step-wise model focused less on subcortical regions such as the thalamus and hippocampus and focused more on distributed cortical pathology. Across the two Step-wise models, 95.1% of TLE patients had accurate classifications in either HC versus TLE and/or L-TLE versus R-TLE tasks. These results included 69.6% of patients being both correctly labelled as TLE and lateralized, 13.9% being correctly labelled TLE but lateralized incorrectly and 11.6% being lateralized correctly but not detected as TLE. These findings provide evidence that diagnostic tasks with simpler, Step-wise AI models may enhance diagnostic performance and interpretability in clinical workflows. Future AI clinical support tools can leverage this step-wise approach in the early identification of TLE-related structural patterns, supporting timely diagnosis and treatment decisions.

Substance use disorder (SUD) is a significant cause of morbidity and mortality among perinatal people. Integrated perinatal SUD treatment programs (SUD, obstetrics, mental health, and other services) show promising improvements in SUD and perinatal outcomes. This study describes the redesign of an integrated perinatal SUD treatment program that partnered with a community-based recovery housing facility to integrate clinical and social services and evaluated the impact of this redesign on several indices of treatment retention.

This retrospective cohort study used health record data from 164 perinatal people aged 18+ years admitted to an integrated intensive outpatient SUD treatment program in Baltimore, Maryland, between March 8, 2021, and June 11, 2025. Negative binomial regression was used to examine the association between the program redesign and length of treatment, and logistic regression was used to examine associations between program redesign and retention (until delivery and at 30-, 60-, and 90-days postpartum).

Perinatal people admitted post-redesign had a 108% increase in length of treatment compared to people admitted pre-redesign (adjusted incidence rate ratios [aIRR] 2.08, 95% CI: 1.40, 3.10). People admitted post-redesign had greater odds of treatment retention until delivery (aOR 3.53, 95% CI: 1.39, 8.95); and greater odds of treatment retention at 30-, 60-, and 90-day postpartum compared to people admitted pre-redesign (adjusted odds ratio [aOR] 6.58, 95% CI: 2.52, 17.16; aOR 9.87, 95% CI: 3.47, 28.07; and aOR 5.50, 95% CI: 1.98, 15.27, respectively).

The study illustrates the benefits of creating community partnerships to deliver integrated clinical and social services to perinatal people with severe forms of SUD.

Non-suicidal self-injury constitutes a significant mental health issue among adolescents due to its association with depressive symptoms, anxiety, and an increased risk of suicidal behavior. Proper assessment of this behavior is essential for both research and clinical practice; however, in the Peruvian context, there are still limited instruments with solid evidence of validity and reliability.

To analyze the psychometric properties of the Inventory of Statements About Self-Injury (ISAS-I) in Peruvian adolescents.

Psychometric, cross-sectional, basic research with a quantitative approach. A total of 1,249 adolescents (56% male) participated and completed a sociodemographic questionnaire and three psychological instruments. The existing Spanish adaptation of the ISAS-I was used, and its content validity and comprehensibility were examined in the target population. Statistical analyses were conducted using structural equation modeling and item response theory.

The ISAS-I demonstrated adequate content validity (V > 0.70), a unidimensional structure (CFI = 0.97, RMSEA = 0.04 [90% CI: 0.041, 0.053], SRMR = 0.04), and adequate reliability (ω = 0.84, H = 0.90, r_xx  = 0.76). In addition, measurement invariance across sex was found (ΔCFI < 0.010 and ΔSRMR < 0.030), along with statistically significant associations with depressive symptoms and generalized anxiety. Item 7 showed the greatest discrimination and information capacity, and the scale demonstrated particular precision at higher levels of non-suicidal self-injury.

The ISAS-I presents adequate evidence of validity and reliability in Peruvian adolescents, supporting its use as a brief and precise measure for assessing non-suicidal self-injury. These findings should be understood as psychometric evidence for the existing Spanish adaptation of the ISAS-I in this population, rather than as evidence of a new cross-cultural adaptation. Furthermore, its invariance across sex and its associations with mental health indicators support its utility in both clinical and research settings, promoting early detection and the design of preventive strategies in adolescent populations.

Delirium, a serious neuropsychiatric hospitalization complication, is a manifestation of underlying neurocognitive vulnerability rather than an acute event. In Japan, a nationwide medical policy mandates early hospital-wide delirium risk screening to evaluate predefined risk factors in inpatient populations. We aimed to identify demographic and clinical factors independently associated with referral-based, consultation-confirmed delirium.

We conducted a retrospective observational study of consecutive hospitalized patients at Nara Medical University Hospital between June 2022 and November 2023, without exclusion criteria. Delirium risk factors were assessed within 3 days of admission using a standardized checklist based on national criteria. Delirium was diagnosed following specialist consultation according to the International Classification of Diseases, 10th Revision (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria. Logistic regression analyses were performed to identify independent association with consultation-confirmed delirium.

Among 20,980 patients (mean age, 67.1 ± 17.0 years; males, 55.0%), 209 (1.0%) were diagnosed with delirium following specialist consultation. Overall, 56.4% met at least one predefined risk criterion at admission. In multivariable analyses adjusted for age and sex, dementia (odds ratio [OR], 3.995; 95% confidence interval [CI], 2.647-6.029), history of delirium (OR, 3.649; 95% CI, 2.158-6.170), and heavy alcohol use (OR, 1.648; 95% CI, 1.002-2.710) were independently associated with consultation-confirmed delirium.

In this large cohort evaluated under a nationwide screening framework, consultation-confirmed delirium was independently associated with baseline neurocognitive vulnerability (dementia and history of delirium) and heavy alcohol use, rather than chronological age alone, supporting vulnerability-focused risk stratification in routine clinical practice.

[This corrects the article DOI: 10.1016/j.conctc.2025.101576.].

Repetitive transcranial magnetic stimulation (rTMS) is an effective, non-invasive treatment option for treatment-resistant posttraumatic stress disorder (TR PTSD) and treatment-resistant depression (TRD). This study assesses left-sided high-frequency (LSHF) rTMS on symptoms of Canadian Armed Forces (CAF) and Royal Canadian Mounted Police (RCMP) members with TRD and TR PTSD at the Carewest Operational Stress Injury clinic.

This feasibility study used a quantitative longitudinal design. The study population included 28 CAF and RCMP members with TR PTSD and TRD, defined as lack of response to two antidepressants and one evidence-based psychotherapy. Patients concurrently undertook biological and psychological treatment as usual. Up to 30 sessions of LSHF rTMS were provided; non-responders switched to right-sided low-frequency (RSLF) rTMS after 20 sessions. Depression and PTSD symptoms were quantified using the PTSD Checklist for DSM-5 (PCL-5) and Patient Health Questionnaire-9 (PHQ-9) before treatment, every 10th session, and at completion. Outcomes were analyzed with one-way repeated-measures analysis of variance.

PHQ-9 scores decreased (p < 0.001) during rTMS treatment, from moderately severe depression at baseline (mean = 18) to moderate depression at the 20th (mean = 11) and 30th (mean = 10) sessions. Similarly, PCL-5 scores significantly decreased (p < 0.001), reaching sub-clinical threshold (initial mean = 48, 20th session mean = 33, and 30th session, mean = 31).

These findings support the efficacy of rTMS for reducing symptoms of TRD and TR PTSD in this population. Larger studies with sham rTMS comparison, blinding, and randomization are needed.